FAQ: Research Project: Excessive Body Weight and Ovarian Cancer
- Why study excessive body weight and ovarian cancer?
More than one-third of adults in the United States have excessive body weight.2 Excessive body weight is more common in Hispanics/Latinos compared to Caucasians and more common in counties with more poverty compared to counties with more wealth.3, 4, 5, 6, 7 Excessive body weight increases a person’s risk for getting cancer.8 Excessive body weight also influences cancer tumor growth and can lead to worse outcomes.8 - Why focus on fat cells?
The hypothesis of this project is that fat cells are an important component of the tumor microenvironment that can affect how a tumor grows and spreads, and may contribute to chemotherapy not working as well. The tumor microenvironment is the area of the body that surrounds the tumor.
This project focuses on NF-kB (nuclear factor kappa light chain enhancer of activated B cells), a protein that controls the expression of genes involved in inflammation and cell survival. Studies show that a high fat diet and excessive body weight activate NF-kB and trigger inflammation.9, 10 - How is the project being conducted?
This project uses mice that are put on a high fat diet to create excessive body weight. Using human cell lines, tumors will be generated in mice with normal body weight and mice with excessive body weight. This project will use these mice to clarify what factors (signaling proteins, inflammatory cytokines, immune cells, metabolites, etc.) are different in tumors from mice with normal versus excess body weight. This project is important because mice that have been genetically engineered to mimic excessive body weight in humans display many of the same pathologies as human patients with excessive body weight and can help identify ways to prevent tumor growth. - What is the potential impact of this project?
By understanding which specific signaling molecules within the complex environment of the tumor promote survival of ovarian cancer cells, researchers can identify new ways to overcome resistance to chemotherapy and prevent cancer from coming back. These studies may also lead to better ways to identify whether a person is at risk for aggressive cancer or for chemotherapy not working.
1 National Ovarian Cancer Coalition. “What is Ovarian Cancer?” NOCC. http://ovarian.org/about-ovarian-cancer/what-is-ovarian-cancer (accessed June 14, 2019)
2 James PT. Obesity: the worldwide epidemic. Clin Dermatol. 2004;22(4):276-280.
3 Levine JA. Poverty and obesity in the U.S. Diabetes. 2011;60(11):2667-2668.
4 Ogden CL, Carroll MD, Fryar CD, Flegal KM. Prevalence of Obesity Among Adults and Youth: United States, 2011-2014. NCHS Data Brief. 2015(219):1-8.
5 Kyrgiou M, Kalliala I, Markozannes G, et al. Adiposity and cancer at major anatomical sites: umbrella review of the literature. BMJ. 2017;356:j477.
6 Aune D, Navarro Rosenblatt DA, Chan DS, et al. Anthropometric factors and ovarian cancer risk: a systematic review and nonlinear dose-response meta-analysis of prospective studies. Int J Cancer. 2015;136(8):1888-1898.
7 Cancer CGoESoO. Ovarian cancer and body size: individual participant meta-analysis including 25,157 women with ovarian cancer from 47 epidemiological studies. PLoS Med. 2012;9(4):e1001200.
8 Kato S, Abarzua-Catalan L, Trigo C, et al. Leptin stimulates migration and invasion and maintains cancer stem-like properties in ovarian cancer cells: an explanation for poor outcomes in obese women. Oncotarget. 2015;6(25):21100-21119.
9 Carlsen H, Haugen F, Zadelaar S, et al. Diet-induced obesity increases NF-kappaB signaling in reporter mice. Genes Nutr. 2009;4(3):215-222.
10 Shankar E, Bhaskaran N, MacLennan GT, Liu G, Daneshgari F, Gupta S. Inflammatory Signaling Involved in High-Fat Diet Induced Prostate Diseases. J Urol Res. 2015;2(1).